Pharmacodynamics and pharmacokinetics of A-80556 using microdialysis in a Streptococcus pneumoniae meningitis model

Using microdialysis in a rabbit model of Streptococcus pneumoniae meningitis, the pharmacokinetics and pharmacodynamics of a new fluoroquinolone, A-80556, were determined. A-80556 (10 mg/kg iv) was administered to four rabbits. Saline was given to four separate control animals. A microdialysis probe perfused the CSF (2 μL/min) and effluent was collected at 0–0.25, 0.25–1, 1–2, 2–4, and 4–6 h after injection of A-80556. Seven blood samples were collected and analyzed by HPLC. At 0, 2, 4, and 6h 300 μL of CSF was withdrawn for pharmacodynamic measurements. Plasma A-80556 concentrations demonstrated AUC0–∞.K 2.40 ± 0.272 μg.h/mL; T½β 1.07 ± 0.011 h; Vd 6.35 ± 0.50 L/kg; and Cl 4.23 ± 0.48 L/h.kg. Penetration into the CSF was 18.21%. Pharmacodynamics using time-kill curves showed a 3-log reduction in bacterial counts in CSF at 2 h after administration continuing for the remaining four hours of the experiment. These results demonstrate that microdialysis can be used for determination of drug penetration and efficacy in experimental S;. pneumoniae meningitis.